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The question remains whether the true information from the recently failed clinical trials of ceftriaxone and olesoxime lies in the fact that the overall clinical care of patients with ALS has significantly altered, at this point in time, disease trajectory for patients. I believe a careful analysis of these "failed" trials might suggest that the disease trajectory over the time in the clinical trial may be different from that projected at the original design of the clinical trial. If this is true, then the good news might be that we are at a point where longer trial times are necessary, similar to the early days of breast cancer treatment in the past.

Some may look at recent failures and be discouraged. In contrast, I think this is a time of unprecedented hope and excitement in ALS research. Thanks in large part to advances in genetics, we understand the disease better than ever. We can now identify a genetic cause for ALS in 15-20 percent of our patients. We are starting to identify subtypes of ALS, which I personally believe is necessary for us to find disease-modifying therapy that makes a large difference. For example, we have genetic subtypes which may respond to antisense oligomers. We have overactivation in the co-stimulatory pathway in a subset of patients with sporadic ALS, which should soon allow us to target this subset with specific immunomodulators. We have surrogate biomarkers, such as this co-stimulatory pathway, that can at least tell us whether we are hitting our targeted mechanism with the drug and dosing regimens we choose, and we have evaluative biomarkers such as electrical impedence myography that allow us to follow patients more efficiently (meaning we should be able to do smaller, shorter duration studies). We have more potential ALS targets than ever before (transcription, translation, protein aggregation, mitochondria, neuroinflammation, axonal sprouting, muscle contraction), and creative ways to manipulate these. We have novel and unique partnerships with patients to identify promising drugs and supplements that warrant further and more traditional study (such as ALSUntangled and patient-led trials on PatientsLikeMe), and to tackle barriers to enrollment in our studies (such as the ALS Clinical Research Learning Institute). We have never been closer to finding meaningful ALS drug therapies than we are today.

The multimodality of transplanted neural stem cells may also be a feature of endogenous neural stem cells; thus, factors that promote endogenous neural stem cell generation may have comparable benefit.